ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Zijian Li,Hufei Wang,Xiao Liu,Zhengyang Chang,Jianpeng Gao,Junyao Cheng,Licheng Zhang,Xing Wang,Ming Li,Jianheng Liu,Peifu Tang
Achilles tendon injuries present significant clinical challenges due to limited regenerative capacity and frequent adhesion formation. Here, we report a melatonin-loaded Janus fibrous membrane (MLT@JFM) that mimics the native paratenon’s structure and function to promote scarless tendon healing. The biomimetic membrane consists of an inner methacrylated silk fibroin (SFMA) layer that promotes tendon stem cell functions and an outer melatonin-loaded polycaprolactone methacryloyl (PCLMA) layer that prevents adhesion formation. Through photo-cross-linking and structural interlocking, MLT@JFM achieves excellent mechanical properties and stable fixation around injured tendons. In vitro studies demonstrate that MLT@JFM effectively scavenges reactive oxygen species, modulates macrophage polarization, and maintains tendon stem cell phenotype under inflammatory conditions. In a rat Achilles tendon injury model, MLT@JFM significantly enhances functional recovery and biomechanical properties while preventing adhesion formation. Transcriptomic analysis reveals that MLT@JFM promotes scarless healing through synergistic regulation of oxidative-inflammatory cascades and the enhancement of tissue regeneration. This study presents MLT@JFM as a promising therapeutic strategy for tendon repair and provides new insights into biomaterial-mediated tissue regeneration.
研究领域:
生物材料
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组织工程
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再生医学
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2022
·
IF 0
Daisy M. Ramos,Sama Abdulmalik,Michael R. Arul,Naseem Sardashti,Yeshavanth Kumar Banasavadi-Siddegowda,Syam P. Nukavarapu,Hicham Drissi,Sangamesh G. Kumbar
Approximately half of annual musculoskeletal injuries in the US involve tendon tears. The naturally hypocellular and hypovascular tendon environment makes tendons injury-prone and heal slowly. Tendon tissue engineering strategies often use biomimetic scaffolds combined with bioactive factors and/or cells to enhance healing. FDA-approved growth factors to promote tendon healing are lacking, which highlights the need for safe and effective bioactive factors. Our previous work evaluated insulin as a bioactive factor and identified an optimal dose to promote in vitro mesenchymal stem cell survival, division, and tenogenesis. The present work evaluates the ability of insulin-functionalized electrospun nanofiber matrices with or without mesenchymal stem cells to enhance tendon repair in a rat Achilles injury model. Electrospun nanofiber matrices were functionalized with insulin, cultured with or without mesenchymal stem cells, and sutured to transected Achilles tendons in rats. We analyzed rat tendons 4 and 8 weeks after surgery for the tendon morphology, collagen production, and mechanical properties. Bioactive insulin-functionalized fiber matrices with mesenchymal stem cells resulted in significantly increased collagen I and III at 4 and 8 weeks postsurgery. Additionally, these matrices supported highly aligned collagen fibrils in the regenerated tendon tissue at 8 weeks. However, treatment- and control-regenerated tissues had similar tensile properties at 8 weeks, which were less than that of the native Achilles tendon. Our preliminary results establish the benefits of insulin-functionalized fiber matrices in promoting higher levels of collagen synthesis and alignment needed for functional recovery of tendon repair.
研究领域:
再生医学
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组织工程
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生物材料科学
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DOI
PubMed
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2022
·Vol. 111
·期 2
·170-184
·
IF 4.854
Can Cheng,Xu Peng,Linjie Xi,Yihao Luo,Yuhang Wang,Yufan Zhou,Xixun Yu
Naringin (Nar), a natural flavanone glycoside, has been shown to possess a variety of biological activities, including anti-inflammatory, anti-apoptotic, bone formation, and so forth. In this study, Nar was oxidized by sodium periodate and the oxidized naringin (ONar) was used as a novel biological crosslinking agent. In addition, ONar-fixed porcine decellularized Achilles tendon (DAT) was developed to substitute anterior cruciate ligament (ACL) for researching a novel ACL replacement material. The ONar with a 24 h oxidation time had appropriate aldehyde group content, almost no cytotoxicity, and a good crosslinking effect. The critical characteristics and cytocompatibility of ONar-fixed DAT were also investigated. The results demonstrated that 1% ONar-fixed DAT exhibited good resistance to enzymatic degradation and thermal stability as well as suitable mechanical strength. Moreover, 1% ONar-fixed specimens exhibited excellent L929 fibroblasts-cytocompatibility and MC3T3-E1-cytocompatibility. They also promoted the secretion of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) from fibroblasts and bone morphogenetic protein-2 (BMP-2) from osteoblasts. And they also showed the good anti-inflammatory properties in vivo experiments. Our data provided an experimental basis for ONar as a new cross-linking reagent in chemical modification of DAT and ONar-fixed DAT for ACL repair.
研究领域:
生物医学工程
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组织工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Tissue Engineering Part A
·
2021
·
IF 3.845
Hang Zhang,Zijie Pei,Changbao Wang,Mingshan Li,Hongtao Zhang,Jing Qu
Tissue engineering (TE) studies for Achilles tendon (AT) defects are a difficult and popular field in orthopedic medical practice. In this study, we applied electrohydrodynamic three-dimensional (3D) printing technology to construct scaffolds made of poly-(ɛ-ɛ-caprolactone) (PCL) and Pluronic F127 (F127) with different mass-volume ratios. The fibers and porous capabilities of the scaffolds were controlled using this technology. We found that F127 improved the hydrophilicity and degradation of PCL in vitro. The PCL scaffolds with 5% F127 were mostly favorable for cell adhesion and growth, suggesting that the scaffolds had good biocompatibility in vitro. Scaffolds with 5% F127 seeded with C3H10T1/2 cells were transplanted into AT defects in rats. A histological analysis indicated that the TE scaffolds were beneficial for the accumulation and arrangement of collagen fibers. Thus, this study provides fundamental experimental data for future clinical applications regarding TE for ATs.Impact statementElectrohydrodynamic three-dimensional (3D) printing can be used to construct tissue-engineered scaffolds with controllable fibers and good porosity. Pluronic-F127 (F127) improved the hydrophilicity and degradation of the poly-(ɛ-ɛ-caprolactone) (PCL), and a better microscale structure was obtained. The scaffolds with 5% F127, with good pore structures, were favorable for C3H10T1/2 cell growth and cellular morphology, indicating that they had good biocompatibility. In vivo transplantation experiments showed that scaffolds with 5% F127 improved the arrangement of collagen fibers, encouraging their potential application in the construction of future tissue-engineered tendons.
研究领域:
骨科
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组织工程
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生物医学工程
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Zhang Jinchi,Zhang Xiaowei,Li Wei,Guo Jing,Yang Liqun,Yan Guangqi
Introduction: In this study, Poly (trimethylene carbonate)/Doxycycline hydrochloride (PTMC/DH) films were introduced to repair the Achilles tendon defects for the first time.Methods: (PTMC/DH) films with different DH content of 10, 20, and 30% (w/w) were prepared by solvent casting. The in vitro and in vivo drug release of the prepared PTMC/DH films was investigated.Results: The results of drug release experiments showed that the PTMC/DH films released effective concentrations of doxycycline for more than 7 and 28 days in vitro and in vivo, respectively. The results of antibacterial activity experiments showed diameters of 25.00 ± 1.00 mm, 29.33 ± 1.15 mm, and 34.67 ± 1.53 mm, respectively, for the inhibition zones produced by the release solutions of PTMC/DH films with 10, 20 and 30% (w/w) DH at 2 h, indicating that the drug-loaded films could inhibit Staphylococcus aureus well. After treatment, the Achilles tendon defects have recovered well, as indicated by the more robust biomechanical properties and the lower fibroblast density of the repaired Achilles tendons. Pathology revealed that the pro-inflammatory cytokine, IL-1β, and the anti-inflammatory factor, TGF-β1, peaked in the first three days and gradually decreased as the drug was released more slowly.Discussion: These results demonstrated that the PTMC/DH films have great potential for regenerating Achilles tendon defects.
研究领域:
生物医学工程
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药理学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yu Wei,Xing Yun,Yanjun Guan,Shunze Cao,Xiangling Li,Yu Wang,Haoye Meng,Yujie Liu,Qi Quan,Min Wei
Inflammation is part of the natural healing response, but persistent inflammatory events tend to contribute to pathology changes of tendon or ligament. Phenotypic switching of macrophages within the inflammatory niche is crucial for tendon healing. One viable strategy to improve the functional and biomechanical properties of ruptured tendons is to modulate the transition from inflammatory to regenerative signals during tendon regeneration at the site of injury. Here, we developed a tendon repair scaffold made of biodegradable polycaprolactone by electrospinning, which was modified to deliver Wnt3a protein and served as an implant to improve tendon healing in a rat model of Achilles tendon defect. During the in vitro study, Wnt3a protein promoted the polarization of M2 macrophages. In the in vivo experiment, Wnt3a scaffold promoted the early recruitment and counting curve of macrophages and increased the proportion of M2 macrophages. Achilles function index and mechanical properties showed that the implantation effect of the Wnt3a group was better than that of the control group. We believe that this type of scaffold can be used to repair tendon defects. This work highlights the beneficial role of local delivery of biological factors in directing inflammatory responses toward regenerative strategies in tendon healing.
研究领域:
生物材料
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组织工程
·
再生医学
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炎症生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Anlong Liu,Qi Wang,Zinan Zhao,Rui Wu,Maochun Wang,Jiawei Li,Kuoyang Sun,Ziying Sun,Zhongyang Lv,Jia Xu,Huiming Jiang,Mimi Wan,Dongquan Shi,Chun Mao
The microneedle (MN) provides a promising strategy for transdermal delivery of exosomes (EXO), in which the therapeutic effects and clinical applications are greatly reduced by the fact that EXO can only partially reach the injury site by passive diffusion. Here, we designed a detachable MN array to deliver EXO modified by a nitric oxide nanomotor (EXO/MBA) for Achilles tendinopathy (AT) healing. With the releasing of EXO/MBA, l-arginine was converted to nitric oxide by NOS or ROS as the driving force. Benefiting from the motion ability and the property of MPC tending to lower pH, EXO could accumulate at the injury site more efficiently. This work demonstrated that EXO/MBA-loaded MN notably suppressed the inflammation of AT, facilitated the proliferation of tendon cells, increased the expression of Col1a, and prevented extracellular matrix degradation, indicating its potential value in enthesiopathy healing and other related biomedical fields.
研究领域:
生物医学工程
·
药学
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组织工程
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 40
·
IF 11.7
Yijie Fang,Dantian Zhu,Jingyue Wei,Lei Qian,Rongmao Qiu,Taoyu Jia,Kui Huang,Suwen Zhao,Jun Ouyang,Man Li,Shaolin Li,Yang Li
Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons’ collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis.
研究领域:
运动医学
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生物力学
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分子生物学
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医学影像学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2022
·
IF 1.798
Kai KANG,Lukuan CUI,Qian ZHANG,Shijun GAO
Although many surgical or non-operative therapies have been developed to treat Achilles tendon injuries, the prognosis of which is often unsatisfactory. Recently, biologic approaches using multipotent stem cells like tendon-derived stem cells (TDSCs) pose a possible treatment option. To evaluate whether the Leucine rich repeat containing 32 (Lrrc32) affects the tenogenic differentiation of TDSCs and thus promotes Achilles tendon healing. TDSCs were infected with the recombinant Lrrc32-overexpressing lentivirus (LV-Lrrc32) and then locally injected into the injured site of rat. Four weeks after surgery, the Achilles tendon tissue (~0.5 cm) around the injured area was harvested for analysis. Pathological results showed that Lrrc32-overexpressing TDSCs significantly improved the morphological changes of the injured tendons. Specifically, the increased collagen-I expression and hydroxyproline content in extracellular matrix, and more orderly arrangement of the regenerated collagen fibers were observed in the Lrrc32 overexpression group. Moreover, 4 weeks after injection of Lrrc32-overexpressing TDSCs, the expression of tenocyte-related genes such as tenomodulin (Tnmd), scleraxis (Scx) and decorin (Dcn) were upregulated in the area of the healing tendon. These findings indicated that Lrrc32 promoted the tenogenic differentiation of TDSCs in vivo. Additionally, Lrrc32 overexpression also increased the expression of TGF-β1 and p-SMAD2/3, suggesting that the beneficial effects of Lrrc32 on tendon repair might be associated with the expression of TGF-β1 and p-SMAD2/3. Our findings collectively revealed that Lrrc32-overexpressed TDSCs promoted tendon healing more effectively than TDSCs alone.
研究领域:
干细胞生物学
·
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2022
·
IF 3.511
Qinghui Han,Shuguang Wang,Dawei Chen,Di Gan,Tao Wang
Tendon injuries are common clinical issues resulted from tissue overuse and age-related degeneration. Previous sutdies have suggested that exosomes secreted by mesenchymal stem cells (MSCs) contribute to tissue injury repair. Here, we provide evidence for a critical role of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes in reducing tendon injury by activating the RhoA signaling. Treatment of primary injured tenocytes with hucMSC exosomes increases cell proliferation and invasion, which correlates with increased RhoA activity. RhoA mediates the effects of hucMSC exosomes, as treatment of primary injured tenocytes with the RhoA inhibitor, CCG-1423, abolishes the effects of hucMSC exosomes on cell proliferation and invasion. Mechanistically, we observe that hucMSC exosomes induce the expression of a microRNA, miR-27b-3p, which targets and suppresses ARHGAP5, a negative regulator of RhoA. Consistent with this observation, ARHGAP5 overexpression suppresses the effects of hucMSC exosomes on cell proliferation and invasion, while knockdown of ARHGAP5 rescues these effects. Finally, we demonstrate the functional significance of our findings in vivo using an Achilles tendon injury model and show that treatment with exosomes reduces tendon injury in rats, which correlates with increased RhoA activity and reduced ARHGAP5 expression. Taken together, our findings highlight a critical role of hucMSC exosomes in reducing tendon injury via miR-27b-3p-mediated suppression of ARHGAP5, resulting in RhoA activation, and leading to increased cell proliferation and invasion of primary injured tenocytes.
研究领域:
干细胞生物学
·
分子生物学
·
再生医学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Han Qibin,Bai Lang,Qian Yinhua,Zhang Xiaoyu,Wang Juan,Zhou Jing,Cui Wenguo,Hao Yuefeng,Yang Xing
Tendinopathy is a common disorder that causes local dysfunction and reduces quality of life. Recent research has indicated that alterations in the inflammatory microenvironment play a vital role in the pathogenesis of tendinopathy. Herein, injectable methacrylate gelatin (GelMA) microspheres (GM) were fabricated and loaded with heparin-dopamine conjugate (HDC) and hepatocyte growth factor (HGF). GM@HDC@HGF were designed to balance the inflammatory microenvironment by inhibiting oxidative stress and inflammation, thereby regulating extracellular matrix (ECM) metabolism and halting tendon degeneration. Combining growth factors with heparin was expected to improve the encapsulation rate and maintain the long-term efficacy of HGF. In addition, the catechol groups on dopamine have adhesion and antioxidant properties, allowing potential attachment at the injured site, and better function synergized with HGF. GM@HDC@HGF injected in situ in rat Achilles tendinopathy (AT) models significantly down-regulated oxidative stress and inflammation, and ameliorated ECM degradation. In conclusion, the multifunctional platform developed presents a promising alternative for the treatment of tendinopathy.
研究领域:
生物医学工程
·
药理学
·
组织工程
·
炎症生物学
✓ 已验证
DOI
PubMed
高影响因子
Science China-Chemistry
·
2015
·Vol. 58
·期 7
·1159-1168
·
IF 1.695
Song Zhiming,Shi Bo,Ding Jianxun,Zhuang Xiuli,Zhang Xiaonan,Fu Changfeng,Chen Xuesi
Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly( L -lactide) (PLA) and poly(ε-caprolactone) (PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media (i.e., phosphate-buffered saline) maintained at a constant pH of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson’s trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.
研究领域:
生物材料
·
组织工程
·
骨科手术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）